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Investigating the role of NEK1 in amyotrophic lateral sclerosis (ALS)

Project Description

Project details:
Amyotrophic Lateral Sclerosis (ALS) is an aggressive neurodegenerative disease with no effective therapy. It is characterised by selective loss of motor neurons in the spinal cord and cortex.
Heterozygous loss-of-function (LOF) mutations in NEK1 are a cause of familial and sporadic ALS, and nonsynonymous and LOF mutations in the NEK1 interacting mitochondrial protein C21orf2 are associated with increased ALS risk. Both NEK1 and C21orf2 are involved in DNA damage repair, but have also been implicated in signalling between the nucleus and mitochondria in response to DNA damage; how their loss causes ALS remains unclear.
ER-mitochondria contacts are inter-organelle contact sites that have been shown to regulate several physiological processes that have been implicated in ALS including autophagy, calcium homeostasis, and synaptic function. Reduced ER- mitochondria coupling and signalling has been reported in multiple forms of ALS, including ALS associated with mutations in SOD1, TDP-43, FUS, and Sigma-1R.
In this project we will investigate how mutations in NEK1 and C21orf2 cause ALS, with particular focus on the possible role of ER-mitochondria contacts.

You will be receiving a broad training in molecular and cellular neurobiology. This will include (neuronal) cell culture, protein biochemistry (immunoblots, immunoprecipitation, in vitro binding assay, phosphorylation assays), molecular biology (cloning, mutagenesis), microscopy (fluorescence, live (calcium) imaging, confocal, super-resolution, electron microscopy) and neuronal cell biology techniques (synaptic function assays, multi electrode arrays, axonal transport).

You will be supervised by Prof Kurt De Vos and Dr Andrew Grierson (Dept. of Neuroscience). You will join our collaborative, supportive and tight-knit research groups and wider communities with the SITraN research centre. You will also join an active, friendly and lively PhD student cohort at SITraN, the Medical School and wider University of Sheffield, which hosts regular social events alongside networking and career development opportunities. We are committed to supporting the career development of our students and encourage attendance at both International and UK meetings, conferences and training courses to develop your research skills and interests.

Funding Notes

This project is funded by an MNDA Prize Studentship (www.mndassociation.org). The studentship provides full support for tuition fees (at UK/EU levels) and a tax-free annual stipend (£16,000-£17,000) for 3 years. Start date is October 2020.

Entry Requirements:
Candidates must have a first or strong upper second-class honors degree or significant research experience.


Interested candidates should in the first instance contact Kurt De Vos ([email protected]; https://www.sheffield.ac.uk/neuroscience/staff/devos; http://sitran.org/people/devos/ )

How to apply:
Please complete a University Postgraduate Research Application form available here: www.shef.ac.uk/postgraduate/research/apply

Please clearly state the prospective main supervisor in the respective box and select 'Neuroscience' as the department.

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